Proton (1H) Nuclear Magnetic Resonance Spectroscopy (MRS) is a potentially powerful, non-invasive, non-destructive analytical tool. 1H-MRS produces complex spectra, which may serve as a potential "fingerprinting" tool for identification of various tissues. The overall goal of this project is to establish 1H-MRS as a useful and meaningful technique for studying skin tumorigenesis and malignant transformation in vivo by determining valid and useful spectral markers or patterns that reflect the stages of carcinogenesis, which potentially can be monitored with tumor metabolism and/or in response to external factors. The most useful and valid markers and patterns reflecting carcinogenesis may be established by studying the aqueous compartments with 1H-MRS not by a single observation in time but by observing induction and promotion of tumors and their malignant transformation, in vivo. Development of this unique non-invasive technique may greatly enhance current concepts of tumor biology, epidemiology, and mechanisms of carcinogenesis. Also, establishment of 1H-MRS markers or patterns that can be monitored non-invasively may allow earlier detection of malignant tumor foci than the conventional modalities. Therefore, this technology would benefit individuals in high-risk groups such as familial dysplastic nevus or melanoma, giant congenital melanocytic nevus, xeroderma pigmentosum, and dystrophic epidermolysis bullosa patients, whose risk for developing malignant tumors is much higher than that in the general population. While the ultimate goal is to perform in vivo analysis, it is necessary to begin with 1H-MRS analysis of tissue extracts. Therefore, the specific aims of this research are to: (1) establish valid 1H-MRS markers or spectral patterns reflecting the stages of carcinogenesis by means of acid extract analysis of tissues from various stages of skin carcinogenesis in animal models (squamous cell carcinoma (SCCa) in mice) and extract analysis of cells and tissues for necessary control comparisons; (2) determine the appropriate coils/probes, measuring and editing methods to correlate the extract findings with in vivo observations; (3) demonstrate the potential of in vivo monitoring of 1H-MRS markers or patterns changes in evolving stages of carcinogenesis of SCCa in mice and with external manipulation (hyperthermia); (4) explore the usefulness of 1H-MRS in studying a experimental model of carcinogenesis using xenografts which has relevance to SCCa development in dystrophic epidermolysis bullosa patients to determine future applicability of this technique for individuals in the high-risk group; (5) compare the effectiveness of 1H-MRS with conventional methods for detection of tumor development and malignant conversion such as visual exam, serial photography, histologic exam of suspicious areas.